Monocyte-derived stem cells

Abstract

Methods for generating multipotent stem cells from adult peripheral blood monocytes are provided. Monocytes may be de-differentiated into monocyte-derived stem cells (MDSCs) by contacting the monocyte with the de-differentation factors, leukocyte inhibitory factor, macrophage colony-stimulating factor, or a combination thereof. The MDSCs may be differentiated into many different types of cells upon contact with the appropriate differentiation factors. Also provided are compositions comprising the MDSCs or differentiated cells derived from the MDSCs.

1 . A method for generating a stem cell, the method comprising:
 (a) providing an isolated monocyte; and   (b) contacting the monocyte with a de-differentiation agent.   
     
     
         2 . The method of  claim 1 , wherein the de-differentiation agent comprises leukocyte inhibitory factor (LIF) or macrophage colony-stimulating factor (M-CSF). 
     
     
         3 . The method of  claim 1 , wherein the stem cell expresses a marker selected from the group consisting of CD117, DPPA5, HES-1, Oct-4, and SSEA4. 
     
     
         4 . The method of  claim 1 , wherein the monocyte is isolated from mammalian peripheral blood. 
     
     
         5 . The method of  claim 4 , wherein the mammal is a human. 
     
     
         6 . The method of  claim 5 , wherein the human is an adult. 
     
     
         7 . The method of  claim 1 , wherein the monocyte does not express a marker selected from the group consisting of CD117, DPPA5, Oct-4, SSEA-4, CD135, and combinations thereof. 
     
     
         8 . The method of  claim 1 , wherein the stem cell expresses a marker selected from the group consisting of CD117, DPPA5, HES-1, Oct-4, SSEA-4, and combinations thereof. 
     
     
         9 . The method of  claim 1 , wherein the stem cell has a characteristic selected from the group consisting of CD11b+, CD 14+, CD34−, CD45+, CD90−, CD117+, DPPA5+, HES-1+, Oct-4+, SSEA-4+, CD135−, and combinations thereof. 
     
     
         10 . The method of  claim 1 , wherein the monocyte and the stem cell are grown in a serum-free medium. 
     
     
         11 . The method of  claim 1 , wherein the stem cell is generated after 4-8 days in culture. 
     
     
         12 . The method of  claim 1 , wherein the stem cell is contacted with a cryopreservative agent and deep-frozen. 
     
     
         13 . An isolated stem cell, wherein the cell expresses a marker selected from the group consisting of CD117, DPPA5, HES-1, Oct-4, SSEA-4, and combinations thereof. 
     
     
         14 . The stem cell of  claim 13 , wherein the stem cell has a characteristic selected from the group consisting of CD11b+, CD14+, CD34−, CD45+, CD90−, CD117+, DPPA5+, HES-1+, Oct-4+, SSEA-4+, CD135−, and combinations thereof. 
     
     
         15 . The stem cell of  claim 13 , wherein the stem cell is derived from an isolated monocyte. 
     
     
         16 . The stem cell of  claim 15 , wherein the monocyte is derived from mammalian peripheral blood. 
     
     
         17 . The stem cell of  claim 16 , wherein the mammal is a human. 
     
     
         18 . The stem cell of  claim 17 , wherein the human is an adult. 
     
     
         19 . The stem cell of  claim 13 , wherein the stem cell is contacted with a cryopreservative agent and deep-frozen. 
     
     
         20 . A composition comprising more than 1×10 6  of the stem cell of  claim 13 .